Single-cell and spatial transcriptomics reveals the key role of MCAM(+) tip-like endothelial cells in osteosarcoma metastasis.

Osteosarcoma, the most common primary malignant bone tumor in children and adolescents, is highly aggressive and prone to metastasis. Endothelial cells (ECs) are involved in angiogenesis and play a key role in promoting the metastasis of tumor. However, research on tip-like ECs within osteosarcoma was extremely rare. In this study, a single-cell atlas of ECs was constructed using single-cell transcriptomic data. It was found that tip-like ECs were abundant in the primary tumors and metastatic foci. Gene sets score analysis indicated their enrichment in pathways associated with angiogenesis and metastasis. What's more, MCAM was highly expressed in tip-like ECs and was likely to promote the metastasis of osteosarcoma. MCAM was also found to be highly expressed in the ECs of metastatic lymph nodes when compared to normal lymph node samples. Meanwhile, spatial transcriptomics data confirmed the presence of MCAM-positive ECs in metastatic lymph node, closely localized to osteoblasts. In vitro assays, including qRT-PCR, tube formation, and immunofluorescence, validated the role of the MCAM gene in promoting angiogenesis. In conclusion, tip-like ECs may promote tumor metastasis by enhancing angiogenesis. MCAM was a functional gene for tip-like ECs and could serve as a target for the treatment of osteosarcoma.